Developmental vascular regression is regulated by a Wnt/β-catenin, MYC and CDKN1A pathway that controls cell proliferation and cell death

Development. 2018 Jun 14;145(12):dev154898. doi: 10.1242/dev.154898.


Normal development requires tight regulation of cell proliferation and cell death. Here, we have investigated these control mechanisms in the hyaloid vessels, a temporary vascular network in the mammalian eye that requires a Wnt/β-catenin response for scheduled regression. We investigated whether the hyaloid Wnt response was linked to the oncogene Myc, and the cyclin-dependent kinase inhibitor CDKN1A (P21), both established regulators of cell cycle progression and cell death. Our analysis showed that the Wnt pathway co-receptors LRP5 and LRP6 have overlapping activities that mediate the Wnt/β-catenin signaling in hyaloid vascular endothelial cells (VECs). We also showed that both Myc and Cdkn1a are downstream of the Wnt response and are required for hyaloid regression but for different reasons. Conditional deletion of Myc in VECs suppressed both proliferation and cell death. By contrast, conditional deletion of Cdkn1a resulted in VEC overproliferation that countered the effects of cell death on regression. When combined with analysis of MYC and CDKN1A protein levels, this analysis suggests that a Wnt/β-catenin and MYC-CDKN1A pathway regulates scheduled hyaloid vessel regression.

Keywords: CDKN1A; Endothelial cell; Hyaloid; MYC; P21; Vascular regression; Wnt signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cell Line
  • Cell Proliferation / physiology*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Eye / blood supply
  • HEK293 Cells
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-5 / metabolism
  • Low Density Lipoprotein Receptor-Related Protein-6 / metabolism
  • Mice
  • Mice, Knockout
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Wnt Signaling Pathway / physiology
  • beta Catenin / metabolism*


  • CTNNB1 protein, mouse
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Lrp5 protein, mouse
  • Lrp6 protein, mouse
  • Myc protein, mouse
  • Proto-Oncogene Proteins c-myc
  • beta Catenin